Use Of GnRH Antagonists Research Articles

GnRH antagonists may affect endometrial receptivity

HOXA10 is an essential regulator of endometrial receptivity. To determine the effect of GnRH antagonists on endometrial receptivity, we assessed endometrial HOXA10 expression in GnRH antagonist, GnRH agonist, and natural cycles. Prospective case-control study. University academic medical center. Nineteen subjects were included: 12 subjects underwent controlled ovarian hyperstimulation with recombinant FSH and used either a GnRH antagonist or a GnRH agonist; seven control subjects underwent natural cycles. Pipelle endometrial biopsies were obtained 11 days after hCG administration or spontaneous LH surge in untreated cycles, respectively. Immunohistochemistry was used to assess HOXA10 protein expression in endometrial glands and stroma. Endometrial HOXA10 protein expression. HOXA10 expression was significantly decreased in endometrial stromal cells in GnRH antagonist-treated cycles compared with GnRH agonist-treated cycles or natural cycle control subjects. There was no significant difference in glandular cell HOXA10 expression among the three groups. Use of GnRH antagonists may be associated with impaired HOXA10 expression in endometrial stromal cells and thus may affect endometrial receptivity.

Embryo aneuploidies in GnRH agonist vs. GnRH antagonist cycles. experience of 2,000 cycles

To determine if the use of GnRH antagonists increases the incidence of embryo aneuploidies with respect to the use of GnRH agonists. Retrospective cohorts study. Analysis of 2,066 Preimplantation Genetic Diagnosis (PGD) cycles performed in our institution for different indications between January 1st 2002 and December 31st 2006. Fluorescent in situ hibridization (FISH) was employed to analyze chromosomes 13, 16, 18, 21, 22, X and Y, in a total of 9,948 embryos. GnRH antagonists were used in 1098 cycles (53.1%), involving 4,412 embryos (44.4%), while GnRH agonists were administered in 968 cycles (46.9%), and included 5,536 embryos (55.6%). Aneuploidies rate plus, pregnancy, implantation and miscarriage rates are compared. Data according to age groups are shown in tables. Table 1 shows results in patients aged ≤39: No significant differences were observed regarding embryo aneuploidies or clinical results. Table 2 shows data of patients ≥40 years old: Patients that received a GnRH antagonist displayed a significantly higher proportion of abnormal embryos, and lower cycle success rates. In patients aged <40 years old, the incidence of embryo aneuploidies observed in GnRH antagonist cycles is comparable to that one observed in GnRH agonists long protocol cycles. In patients >40, the use of a GnRH antagonist was associated with more aneuploid embryos and poorer outcome. This finding may be related to the use of GnRH antagonists in patients with a lower ovarian reserve.

GnRH antagonist prevents premature luteinization in intrauterine insemination cycles: a rationale for its use

There is a great controversy on whether the use of GnRH antagonist are beneficial for patients undergoing intrauterine insemination (IUI), as some but not all authors showed increased cycle outcome. The aim of our study was to determine the prevalence as well as the effect of premature luteinization (PL) in patients undergoing intrauterine insemination, and explore the possibility of improving the outcome of these patients by preventing previous PL with GnRH antagonists.

GnRH antagonist use is associated with increased pregnancy rates in ovulation induction/intrauterine insemination (OI/IUI) to IVF conversions, independent of age and estradiol level at retrieval

GnRH antagonist use is associated with increased pregnancy rates in ovulation induction/intrauterine insemination (OI/IUI) to IVF conversions, independent of age and estradiol level at retrieval

GnRH-agonist vs. GnRH-antagonist in elective single blastocyst transfer IVF cycles

To study whether the implantation potential of embryos produced in a GnRH-agonist cycle would differ from those embryos produced in a GnRH-antagonist cycle. Single embryo transfer setting represents the perfect setting. Case control study. Clinical pregnancy rate at 7 weeks represents implantation rate. Subfertile patients less than 36 years of age attempting their first IVF trial could participate in the study only once. 261 patients initiated stimulation and judged eligible for the study. The GnRH-agonist long protocol started on day 21 of the preceding cycle with intranasal Buserelin (600 mg per day). Gonadotrophins (100–300 IU) were administered after three weeks of down-regulation and once hormones were basal. In the GnRH-antagonist protocol gonadotrophins (100–300 IU) were administered from day 2 of the cycle if the hormonal levels were basal and then the antagonist (ganirelix 0.25 mg daily and in few cases Cetrotide 0.25 mg) started on day 6 of the stimulation. In both protocols the stimulation could only initiate if progesterone was lower than 1.5 ng/L and estradiol lower than 80 ng/ml. Sequential media was used for embryo culture. Clinical pregnancy rate is defined as positive heart beat at 7 weeks of gestation. Values are expressed as mean ± standard error of mean (SEM). Single Day-5 embryo transfer was performed in 225 patients, 105 with GnRH-agonist and 120 with GnRH-antagonist. There was no difference with regards the age (29.9 ± 0.3 vs. 30.0 ± 0.3, P=0.8); the COCs (11.8 ± 0.6 vs. 11.6 ± 0.5, P=0.9); 2PN embryos (7.6 ± 0.4 vs. 6.9 ± 0.3, P=0.2); mean embryo quality (1.3 ± 0.1 vs. 1.3 ± 0.1, P=0.8) and embryo cryopreserved (2.3 ± 0.2 vs. 2.2 ± 0.2, P=0.8). Nevertheless, with the antagonist the duration of stimulation was shorter (10.4 vs. 12.1 days, P<0.0001) and the total dose of gonadotrophins required was significantly lower (1818 vs. 2212 IU, P<0.0001). Clinical pregnancy rate was similar between antagonist and agonist (40.0 vs. 36.2%, OR:1.17; 95% CI:0.68–2.01). The recent study is the first comparison attempted between the two protocols in a SET setting and in blastocyst stage embryo transfers.The implantation potential of blastocysts produced in both GnRH-analogue protocols is absolutely comparable with the further advantage of flexibility, shorter stimulation period and reduced use of gonadotrophins concerning the use of GnRH-antagonist. However, the 4% difference in favor of antagonist in terms of clinical pregnancy rate requires additional investigation.

The effect of luteal phase vaginal estradiol supplementation on the success of in vitro fertilization treatment: a prospective randomized study

To determine whether the use of luteal phase vaginal E(2) supplementation improves clinical pregnancy rates in patients undergoing IVF treatment. Prospective randomized controlled trial. University-based tertiary fertility center. One hundred sixty-six patients undergoing their first cycle of IVF treatment. Patients underwent three different protocols for controlled ovarian hyperstimulation for IVF treatment with long GnRH agonist suppression, use of GnRH antagonist, or a microdose GnRH agonist protocol. Luteal phase support was in the form of IM P. Patients randomized into the study group (n = 84) received E(2) supplementation in the form of vaginal estrace 2 mg twice a day starting on the day of ET. Patients randomized to the control group (n = 82) received no E(2) supplementation. Clinical pregnancy rates. There were no significant differences in the implantation (56/210 [26.7%] vs. 64/203 [31.5%]), clinical pregnancy (42/84 [50%] vs. 52/82 [63.4%]), and ongoing pregnancy rates (40/84 [47.6%] vs. 46/82 [56.1%]) between the study and control groups, respectively. In the subgroup of patients who used the long GnRH agonist suppression protocol, there was a lower clinical pregnancy rate in the study group compared with the control group (27/55 [49.1%] vs. 42/59 [71.2%]). There were, however, no differences in clinical pregnancy rates between the two groups in patients who used either the GnRH antagonist or microdose GnRH agonist protocols. The addition of vaginal E(2) supplementation to routine P supplementation for luteal support does not improve the probability of conception after IVF treatment.

Early cleavage does not predict treatment outcome following the use of GnRH antagonists in women older than 35

To compare the early-cleavage rates and the implantation potential of embryos between the GnRH antagonist and agonist long stimulation protocols in women older than 35 years. Retrospective analysis. Academic medical center. Two hundred twenty patients older than 35 years old underwent IVF. Sixty-eight patients received GnRH antagonist protocol (GnRH antagonist group) and 152 patients received GnRH agonist long stimulation protocol (GnRH agonist group). Early-cleavage rate of zygotes, implantation rate, and pregnancy rate. Early-cleavage rate of zygotes was significantly lower in the GnRH antagonist group than agonist group (21.8% vs. 32.6%, P<.0001). In the GnRH antagonist group, the pregnancy rate was not significantly different between the early-cleavage and late-cleavage subgroups (40.0% vs. 47.4%). In the GnRH agonist group, the pregnancy rate was significantly higher in the early-cleavage subgroup than in the late-cleavage subgroup (61.0% vs. 29.8%, P<.0001). In women older than 35 years, the early-cleavage rate of zygotes is significantly lower in the GnRH antagonist group than the agonist group. Early-cleavage status of zygotes is not a reliable predictor for embryo implantation in patients receiving the GnRH antagonist protocol.

Follicular growth and development under continuous gonadotropin-releasing hormone antagonist administration

Ovarian follicle and cyst formation have been recognized as an advance phenomenon associated with GnRH agonist administration. With the use of GnRH antagonists, pituitary suppression is immediate and no flare effect and follicle growth are expected. We describe two patients who developed a dominant follicle and presumably ovulated in response to hCG triggering under continuous sole administration of a GnRH antagonist. Case report. An IVF unit at a university hospital. Two young healthy female patients undergoing IVF because of male-factor infertility. Continuous daily administration of a GnRH antagonist from menstruation with the aim of achieving ovarian suppression. Endocrine and ultrasound characteristics of follicular growth. Both patients developed a dominant follicle under sole administration of a GnRH antagonist, accompanied by a gradual rise in serum estradiol and endometrial thickness which culminated in a spontaneous LH surge. Ovulation was triggered by hCG and mid-luteal progesterone levels were suggestive of ovulation. We describe for the first time the development of a dominant follicle and presumable ovulation under continuous administration of a GnRH antagonist. Serum gonadotropin concentrations indicate that the pituitary failed to suppress in both patients. The exact mechanism of this phenomenon remains to be elucidated.

Novel follicular-phase gonadotropin-releasing hormone antagonist stimulation protocol for in vitro fertilization in the poor responder

Poor responders continue to be vexing in infertility therapy. By using GnRH antagonists before ovarian stimulation, we demonstrate an improvement in oocyte, embryo, and zygote yield in patients with a prior poor response.

Effect of GnRH antagonists in FSH mildly stimulated intrauterine insemination cycles: a multicentre randomized trial

The usefulness of GnRH antagonists in mild controlled ovarian hyperstimulation (COH) and intrauterine insemination (IUI) cycles is debated. Two-hundred and ninety-nine couples with unexplained or mild male factor infertility were enrolled in this international multicentre randomized controlled trial. Women allocated to the GnRH antagonist group (n=148) received 50 IU recombinant FSH starting on day 3 of the menstrual cycle and Ganirelix 0.25 mg daily starting from the day in which a follicle with a mean diameter of 13-14 mm was visualized at ultrasound. Women allocated to the control group (n=151) were administered only 50 IU recombinant FSH starting on day 3 of the menstrual cycle. Couples were recruited only for their first treatment cycle. The primary outcome was the clinical pregnancy rate per initiated cycle. Baseline characteristics of the two treatment groups were similar. Clinical pregnancy rates per initiated cycle in women who did and did not receive GnRH antagonists were 12.2 and 12.6%, respectively (P=1.00). The relative risk of conception (95% confidence interval) for the use of GnRH antagonists was 1.0 (0.5-1.9). In mild COH and IUI cycles, any benefit of the use of GnRH antagonists in improving pregnancy rates is <2-fold increase.

GnRH antagonist-induced inhibition of the premature LH surge increases pregnancy rates in IUI-stimulated cycles. A prospective randomized trial

Our prospective randomized controlled trial was designed to assess whether the use of GnRH antagonists can improve the success rate of controlled ovarian stimulation (COS)/intrauterine insemination (IUI) treatments, via inhibition of the premature LH rise. A total of 104 patients were randomly divided, using a randomization list, into two groups: in group A (n = 52), recombinant FSH (rFSH) was given with GnRH antagonist Cetrorelix, and in group B (n = 52), the patients received rFSH alone in a manner similar to that of group A. The primary outcome measure was clinical pregnancy rate per couple. The pregnancy rate per patient was 53.8% in group A and 30.8% in group B (P = 0.017). The rate of premature LH surge was 7% in group A and 35% in group B (P < 0.0001). A premature luteinization was observed in two cycles of 144 in group A (1.4%) and in 16 cycles of 154 in group B (10.4%) (P = 0.001). The mean values of LH and progesterone were significantly lower in patients receiving GnRH antagonist than in those who did not (3.3 +/- 3.3 mIU/ml in group A versus 9.9 +/- 7.9 mIU/ml in group B, P < 0.0001, for LH; 1.3 +/- 1.1 ng/ml versus 2.1 +/- 1.9 ng/ml for group A and B, respectively, P < 0.0001, for progesterone). The use of GnRH antagonist in COS/IUI cycles improves pregnancy rate, preventing the premature LH rise and luteinization.

P-829: Use of GnRH antagonists in egg donation cycles is associated with reduced serum estradiol and LH levels compared to agonist cycles with and without LH supplementation, but has no effect on implantation or pregnancy rates

There are several practical advantages to the use of GnRH antagonist (GnRH-ant) in egg donation cycles, but persistent concerns about the potential detrimental effect of antagonists on clinical outcome has kept this type of protocol from gaining widespread acceptance. The aim of this study was to compare cycle stimulation characteristics from GnRH-ant cycles with those utilizing a GnRH agonist (GnRH-a) with or without LH supplementation to investigate the potential relationship of these parameters to clinical outcome.

P-738: 367 intrauterine insemination cycles with or without a GnRH antagonist: A prospective randomized study

Multifollicular recruitment during controlled ovarian hyperstimulation in intrauterine insemination (COH-IUI) can bring about a sudden increase in E2 serum levels that is enough to induce an LH surge while follicular growth is still in progress. Thus, to avoid the risk of an unexpected follicular luteinization, ovulation is generally induced as soon as the leading follicle has reached the 18 mm boundary. However, this decreases the possibilities for gestation since it changes the IUI cycle from multi- to monofollicular. Suppressing gonadotropin-LH release with a GnRH antagonist will prevent premature LH surges and follicle luteinization, and allow us to postpone ovulation. With this in mind, we thought that if pregnancy rates in IUI were related to the number of mature follicles present on the day HCG was indicated and, if the limiting factor for follicular development was premature luteinization, why couldn’t any unexpected LH surge be controlled with a GnRH antagonist during the COH-UIU cycle? Thus, the objective of this study was to determine whether including a GnRH antagonist in COH-IUI cycles would increase pregnancy rates. Prospective randomized study. 367 women (19-38 years old) with primary or secondary infertility were included in this prospective randomized study. PCO and endometriosis were excluded. The patients were randomly (by a computer) assigned to controlled ovarian stimulation with rFSH + the GnRH antagonist (Ganirelix Acetate) initiated when the recruited follicles were ≥16mm (n=184) or with rFSH alone (n=183). Ovulation was induced with HCG 5,000 IU/ i.m. A single insemination was performed, 36-38 hours post-HCG, in both groups. Continuous variables were compared with Student’s t test. The Chi-Squared test and Fisher test were used to compare clinical outcome between the two groups. P 4 follicles ≥16 mm), eight in the antagonist group and six in the control group. A non significant increase in the total amount of rFSH (629.5±358 vs 698.1±310 units) and cycle length (6.9 ±3.3 vs 7.8±2.3) was seen in the GnRH antagonist group with respect to the control group. The mean number of antagonist ampoules used was 2±1.2. The number of mature follicles (2.1±1.3 vs. 1.7±1.09, p<0.05) and pregnancy rates (25% vs. 11%, p<0.05) were significantly higher in patients treated with GnRH antagonist than in the control group, respectively. A similar number of twin pregnancies occurred in both groups (two and three, respectively), but the antagonist group also had one triplet gestation. Adding GnRH antagonist to COH-IUI cycles significantly increases pregnancy rates. This increase seems to be related with the number of follicles recruited, and thus, first, the use of GnRH antagonist is not recommended in monofollicular IUI cycles and, second, the risk of multiple gestations needs to be carefully evaluated.

P-795: Effectiveness of using hMG-low dose hCG-GnRH antagonist protocol with unsuccessful hMG-GnRH antagonist protocol cases (full term pregnancies had not resulted) in-vitro fertilization (IVF) cycles

GnRH antagonist does not create flare-up effects such as are seen with GnRH agonist, and secretion of gonadotropin is immediately controllable. However, a decrease in the number or quality of oocytes extracted occurs as a result of the strong effects of GnRH antagonist in some cases. The purpose of our study was to consider what kind of results can be obtained by using hCG at 50 units from the day of GnRH antagonist use in cases that had not previously reached full term pregnancy using the hMG-GnRH antagonist protocol. Retrospective evaluation using the patient’s previous IVF stimulation attempts as a historical control. The subjects were 14 cases on whom IVF was carried out (28 cycles: 14 cycles with oral contraceptive pill-hMG-GnRH antagonist protocol and 14 cycles with oral contraceptive pill-hMG-low dose hCG-GnRH antagonist protocol). All the cases had been unsuccessful even though the antagonist protocol not using low dose hCG had been carried out (full term pregnancies had not resulted). Regarding the ovulation induction method, an oral contraceptive pill was used from day 3 of menstruation in the cycle prior to extracting the eggs. Ovarian stimulation was started from day 4 after completion of a course of oral contraceptive pills. In both antagonist protocols the type of ovulation induction drug was changed depending on the LH level just before beginning ovarian stimulation. When serum LH was more than 1.5mIU/ml, pure urinary FSH or recombinant FSH was used, and when serum LH was less than 1.5mIU/ml hMG (Humegon, Organon, Osaka) was used. Daily hypodermic injections of Cetrorelix 0.25 mg/day were started from the time the leading follicle reached 14 mm. The treatment regime was changed to hMG (Pergogreen:in a ratio of FSH and LH at one to one) from the day Cetrorelix was started. Urinary hCG at 50 units was used together with hMG from the day that use of Cetrorelix was started in the low dose hCG protocol. When the average diameter of the leading follicle reached 20 mm, the type of ovulation induction drug was changed to hCG at 10000 units. No statistical difference was noted between the two groups for the amount of hMG (no low dose hCG group 2680.4±1039.5 vs low dose hCG group 3235.7±1171.5). However, the mean number of oocytes retrieved was significantly higher in the low dose hCG group (no low dose hCG group 9.7±3.7 vs low dose hCG group 14.6±6.3, p<0.05). The fertilization rate was significantly higher in the low dose hCG group (no low dose hCG group 57.1% vs low dose hCG group 69.6%, p<0.05). The blastomere number on the day 3 was significantly higher in the low dose hCG group (no low dose hCG group 6.0±2.4 vs low dose hCG group 7.0±2.2, p<0.05). Moreover, the blastocyst formation rate was significantly higher in the low dose hCG group (no low dose hCG group 37.5% vs low dose hCG group 63.0%, p<0.05). No statistical difference was noted between the two groups for the clinical pregnancy rate (FHM) per ET (no low dose hCG group 7.7% vs low dose hCG group 33.3%). The results of this study suggest that increases in the number of oocytes extracted, the fertilization rate, the average number of day 3 blastomeres, and blastocyst formation rates can all be increased by using low dose hCG to control the overly strong effectiveness of GnRH antagonist in cases that had not reached full term pregnancy using the GnRH antagonist protocol.

EZC-Prostate Models Offer High Sensitivity and Specificity for Noninvasive Imaging of Prostate Cancer Progression and Androgen Receptor Action

In vivo imaging advances have greatly expanded the use of animal cancer models. Herein, we describe two new models that permit prostate imaging ex vivo, in vivo, and in utero. Further, we show the use of these models for detecting small metastasis and testing reagents that modulate the androgen receptor (AR) axis. A luciferase reporter gene was directed to the prostate epithelium using three composite promoters called human kallikrein 2 (hK2)-E3/P, PSA-E2/P, and ARR2PB, derived from hK2, PSA, and rat probasin regulatory elements, to generate the EZC1, EZC2, and EZC3-prostate mice, respectively. EZC2 and EZC3-prostate display robust expression in the prostate with only minimal detectable expression in other organs, including testes and epididymis. Luciferase expression was detected as early as embryonic day 13 (E13) in the urogenital track. To image prostate cancer progression, lines of EZC mice were bred with prostate cancer models TRAMP and JOCK1, and imaged longitudinally. When crossed with prostate cancer models, EZC3 facilitated detection of metastatic lesions although total prostate luciferase expression was static or reduced due to weakening of AR-regulated promoters. Castration reduced luciferase expression by 90% and 97% in EZC2 and EZC3 mice, respectively, and use of GnRH antagonist also led to extensive inhibition of reporter activity. The EZC-prostate model permits prostate imaging in vivo and should be useful for imaging prostate development, growth, metastasis, and response to treatment noninvasively and longitudinally. These models also provide powerful new reagents for developing improved drugs that inhibit the AR axis.

A randomized controlled trial of increasing recombinant follicle-stimulating hormone after initiating a gonadotropin-releasing hormone antagonist for in vitro fertilization-embryo transfer

Pituitary suppression with a GnRH antagonist before IVF may result in a plateau or decrease in estradiol levels. We sought to investigate the effect of increasing recombinant FSH (rFSH) after starting a GnRH antagonist on estradiol levels, implantation rates, and pregnancy rates. Prospective, randomized multicenter study. Military medical center and private practice. Sixty infertile women undergoing IVF who met the appropriate inclusion criteria. Participants were pretreated with combined oral contraceptives (COCs) and received a dose 150-300 IU of rFSH 5 days after taking their last COC. They were randomly assigned to receive their current dose of rFSH (control group) or an additional 75 IU of rFSH (step-up group) after starting a GnRH antagonist. Daily GnRH antagonist injections were started when the lead follicles were 13-14 mm in diameter and continued until hCG was given when two follicles were >or=18 mm. One to three embryos were transferred 3 or 5 days following oocyte retrieval. Women with PCOS, a body mass index >33, a day 3 FSH >14.1 mIU/mL, or prior poor stimulation were excluded. The primary endpoints of this pilot study were embryo implantation, pregnancy, and livebirth rates. Secondary endpoints included the amount and days of rFSH; number of days of GnRH antagonist use; estradiol levels on the day of GnRH antagonist initiation, day 1 and day 2 after initiation, and on the day of hCG; endometrial stripe thickness; number of follicles; and number of oocytes. No differences were reported within the groups with respect to age, BMI, baseline FSH, use of intracytoplasmic sperm injection, vials of rFSH, number of GnRH antagonist injections, changes in estradiol patterns, or peak estradiol level. The control and step-up groups had similar pregnancies (73.3% vs. 63.3%, P=.41), clinical pregnancies (70.0% vs. 60.0%, P=.42), live births (56.7% vs. 60.0%, P=.8), and implantation rates (50.0% and 39.1%, P=.22). The use of rFSH and a GnRH antagonist in good candidates for IVF resulted in outstanding implantation and pregnancy rates. Increasing the dose of rFSH after starting a GnRH antagonist does not alter the estradiol response or improve the implantation and pregnancy rates.

Gn-RH antagonists in intrauterine insemination: the weekend-free protocol

To compare the results of intrauterine insemination (IUI) when GnRH antagonist was added-to avoid IUI on weekend-with those obtained with the standard IUI protocol. In an IUI program under ovarian stimulation with gonadotropins when one or more follicles of 15-16 mm were seen, if it was not possible for logistic reasons (weekend) to perform the insemination 72 h later, GnRH antagonist was administered until human chorionic gonadotropin (hCG) administration. The IUI was performed on Monday. We compared the results of this IUI "weekend-free'' group with our results in standard IUI cycles, where IUI was performed 36-38 h after reaching optimal follicular growth. Both groups were comparable regarding the main demographic parameters, except for higher estradiol levels, due to the prolonging ovarian stimulation. The per cycle pregnancy rate (PR) were very similar in both groups: 15.7% in the weekend-free IUI versus 16.5% in standard IUI. The multiple pregnancy rate and the hyperstimulation rate were also similar. A non-significant trend to higher high-order multiple pregnancy was observed in the weekend-free IUI. In IUI cycles under ovarian suprastimulation with gonadotrophins, the use of GnRH antagonist allows the manipulation of the follicular development in such a way that it is possible to avoid inseminations on the weekends, without apparently reducing the PR.

S-12 Use of GnRH antagonists

S-12 Use of GnRH antagonists

Follicle Recruitment During Controlled Ovarian Hyperstimulation (COH) for IVF Treatment Cycles Provides Comparable Outcomes to Natural Cycle Follicle Recruitment

Follicle Recruitment During Controlled Ovarian Hyperstimulation (COH) for IVF Treatment Cycles Provides Comparable Outcomes to Natural Cycle Follicle Recruitment

Preventing High Order Multiple Pregnancy During Controlled Ovarian Hyperstimulation and Intrauterine Insemination: A Three Year Experience Using 50 IU Recombinant FSH and GnRH Antagonist

Preventing High Order Multiple Pregnancy During Controlled Ovarian Hyperstimulation and Intrauterine Insemination: A Three Year Experience Using 50 IU Recombinant FSH and GnRH Antagonist